Immunization with radiation-attenuated Plasmodium berghei sporozoites induces liver cCD8alpha+DC that activate CD8+T cells against liver-stage malaria.
PLoS One
; 4(4): e5075, 2009.
Article
em En
| MEDLINE
| ID: mdl-19347042
Immunization with radiation (gamma)-attenuated Plasmodia sporozoites (gamma-spz) confers sterile and long-lasting immunity against malaria liver-stage infection. In the P. berghei gamma-spz model, protection is linked to liver CD8+ T cells that express an effector/memory (T(EM)) phenotype, (CD44(hi)CD45RB(lo)CD62L(lo)), and produce IFN-gamma. However, neither the antigen presenting cells (APC) that activate these CD8+ T(EM) cells nor the site of their induction have been fully investigated. Because conventional (c)CD8alpha+ DC (a subset of CD11c+ DC) are considered the major inducers of CD8+ T cells, in this study we focused primarily on cCD8alpha+ DC from livers of mice immunized with Pb gamma-spz and asked whether the cCD8alpha+ DC might be involved in the activation of CD8+ T(EM) cells. We demonstrate that multiple exposures of mice to Pb gamma-spz lead to a progressive and nearly concurrent accumulation in the liver but not the spleen of both the CD11c+NK1.1(-) DC and CD8+ T(EM) cells. Upon adoptive transfer, liver CD11c+NK1.1(-) DC from Pb gamma-spz-immunized mice induced protective immunity against sporozoite challenge. Moreover, in an in vitro system, liver cCD8alpha(+) DC induced naïve CD8+ T cells to express the CD8+ T(EM) phenotype and to secrete IFN-gamma. The in vitro induction of functional CD8+ T(EM) cells by cCD8alpha+ DC was inhibited by anti-MHC class I and anti-IL-12 mAbs. These data suggest that liver cCD8alpha+ DC present liver-stage antigens to activate CD8+ T(EM) cells, the pre-eminent effectors against pre-erythrocytic malaria. These results provide important implications towards a design of anti-malaria vaccines.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium berghei
/
Ativação Linfocitária
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Vacinas Antimaláricas
/
Linfócitos T CD8-Positivos
/
Hepatopatias
/
Malária
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos